tbuckley/cabot-search huggingface dataset:
Multi-institutional study of the frequency, genomic landscape, and outcome of IDH-mutant glioma in pediatrics
Authors: Kee Kiat Yeo, Sanda Alexandrescu, Jennifer A Cotter, Jayne Vogelzang, Varun Bhave, Marilyn M Li, Jianling Ji, Jamal K Benhamida, Marc K Rosenblum, Tejus A Bale, Nancy Bouvier, Kristiyana Kaneva, Tom Rosenberg, Mary Jane Lim-Fat, Hia Ghosh, Migdalia Martinez, Dolly Aguilera, Amy Smith, Stewart Goldman, Eli L Diamond, Igor Gavrilovic, Tobey J MacDonald, Matthew D Wood, Kellie J Nazemi, AiLien Truong, Andrew Cluster, Keith L Ligon, Kristina Cole, Wenya Linda Bi, Ashley S Margol, Matthias A Karajannis, Karen D Wright
Journal: Neuro-Oncology (2022)

Abstract Background The incidence and biology of IDH1/2 mutations in pediatric gliomas are unclear. Notably, current treatment approaches by pediatric and adult providers vary significantly. We describe the frequency and clinical outcomes of IDH1/2-mutant gliomas in pediatrics. Methods We performed a multi-institutional analysis of the frequency of pediatric IDH1/2-mutant gliomas, identified by next-generation sequencing (NGS). In parallel, we retrospectively reviewed pediatric IDH1/2-mutant gliomas, analyzing clinico-genomic features, treatment approaches, and outcomes. Results Incidence: Among 851 patients with pediatric glioma who underwent NGS, we identified 78 with IDH1/2 mutations. Among patients 0–9 and 10–21 years old, 2/378 (0.5%) and 76/473 (16.1%) had IDH1/2-mutant tumors, respectively. Frequency of IDH mutations was similar between low-grade glioma (52/570, 9.1%) and high-grade glioma (25/277, 9.0%). Four tumors were graded as intermediate histologically, with one IDH1 mutation. Outcome: Seventy-six patients with IDH1/2-mutant glioma had outcome data available. Eighty-four percent of patients with low-grade glioma (LGG) were managed observantly without additional therapy. For low-grade astrocytoma, 5-year progression-free survival (PFS) was 42.9% (95%CI:20.3–63.8) and, despite excellent short-term overall survival (OS), numerous disease-related deaths after year 10 were reported. Patients with high-grade astrocytoma had a 5-year PFS/OS of 36.8% (95%CI:8.8–66.4) and 84% (95%CI:50.1–95.6), respectively. Patients with oligodendroglioma had excellent OS. Conclusions A subset of pediatric gliomas is driven by IDH1/2 mutations, with a higher rate among adolescents. The majority of patients underwent upfront observant management without adjuvant therapy. Findings suggest that the natural history of pediatric IDH1/2-mutant glioma may be similar to that of adults, though additional studies are needed.
Specific in situ inflammatory states associate with progression to renal failure in lupus nephritis
Authors: Rebecca Abraham, Madeleine S. Durkee, Junting Ai, Margaret Veselits, Gabriel Casella, Yuta Asano, Anthony Chang, Kichul Ko, Charles Oshinsky, Emily Peninger, Maryellen L. Giger, Marcus R. Clark
Journal: Journal of Clinical Investigation (2022)

BACKGROUNDIn human lupus nephritis (LN), tubulointerstitial inflammation (TII) on biopsy predicts progression to end-stage renal disease (ESRD). However, only about half of patients with moderate-to-severe TII develop ESRD. We hypothesized that this heterogeneity in outcome reflects different underlying inflammatory states. Therefore, we interrogated renal biopsies from LN longitudinal and cross-sectional cohorts.METHODSData were acquired using conventional and highly multiplexed confocal microscopy. To accurately segment cells across whole biopsies, and to understand their spatial relationships, we developed computational pipelines by training and implementing several deep-learning models and other computer vision techniques.RESULTSHigh B cell densities were associated with protection from ESRD. In contrast, high densities of CD8+, γδ, and other CD4-CD8- T cells were associated with both acute renal failure and progression to ESRD. B cells were often organized into large periglomerular neighborhoods with Tfh cells, while CD4- T cells formed small neighborhoods in the tubulointerstitium, with frequency that predicted progression to ESRD.CONCLUSIONThese data reveal that specific in situ inflammatory states are associated with refractory and progressive renal disease.FUNDINGThis study was funded by the NIH Autoimmunity Centers of Excellence (AI082724), Department of Defense (LRI180083), Alliance for Lupus Research, and NIH awards (S10-OD025081, S10-RR021039, and P30-CA14599).
Improving Efficiency in Medical Diagnosis
Authors: Leila Agha, Jonathan Skinner, David Chan
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
FDG PET/CT in Eosinophilic Solid and Cystic Renal Cell Carcinoma With Lung Metastases
Authors: Jun Zhang, Aisheng Dong, Yang Wang
Journal: Clinical Nuclear Medicine (2022)

Abstract Eosinophilic solid and cystic renal cell carcinoma is a recently described emerging renal tumor. Usefulness of FDG PET/CT in the management of eosinophilic solid and cystic renal cell carcinoma has been rarely reported. We describe FDG PET/CT findings in a case of eosinophilic solid and cystic renal cell carcinoma with lung metastases. The primary renal tumor and its metastases showed intense FDG uptake with SUV max of 29.3 for the primary tumor and 21 for the lung metastases.
Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin
Authors: HoJin Shin, Sebastian Schneeweiss, Robert J. Glynn, Elisabetta Patorno
Journal: Annals of Internal Medicine (2022)

Evidence on the risk for cardiovascular events associated with use of first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with metformin is limited.To assess cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with SGLT-2i versus metformin.Population-based cohort study.Claims data from 2 large U.S. commercial and Medicare databases (April 2013 to March 2020).Patients with T2D aged 18 years and older (>65 years in Medicare) initiating treatment with SGLT-2i or metformin during April 2013 to March 2020, without any use of antidiabetic medications before cohort entry, were identified. After 1:2 propensity score matching in each database, pooled hazard ratios (HRs) and 95% CIs were reported.First-line SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin.Primary outcomes were a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke or all-cause mortality (MI/stroke/mortality), and a composite of hospitalization for heart failure (HHF) or all-cause mortality (HHF/mortality). Safety outcomes including genital infections were assessed.Among 8613 first-line SGLT-2i initiators matched to 17 226 metformin initiators, SGLT-2i initiators had a similar risk for MI/stroke/mortality (HR, 0.96; 95% CI, 0.77 to 1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66 to 0.97) during a mean follow-up of 12 months. Initiators receiving SGLT-2i showed a lower risk for HHF (HR, 0.78; CI, 0.63 to 0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48 to 1.00), and similar risk for stroke, mortality, and MI/stroke/HHF/mortality compared with metformin. Initiators receiving SGLT-2i had a higher risk for genital infections (HR, 2.19; CI, 1.91 to 2.51) and otherwise similar safety as those receiving metformin.Treatment selection was not randomized.As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin.Brigham and Women's Hospital and Harvard Medical School.
Association of Race and Socioeconomic Disadvantage With Missed Telemedicine Visits for Pediatric Patients During the COVID-19 Pandemic
Authors: Evan Brociner, Kun-Hsing Yu, Isaac S. Kohane, McGreggor Crowley
Journal: JAMA Pediatrics (2022)

This comparative effectiveness study examines whether race and ethnicity and socioeconomic disadvantage are factors associated with missing telemedicine visits during the COVID-19 pandemic among pediatric patients in Massachusetts.
Trials, Tribunals, and Opportunities for Lung Cancer <i>KRASG12C</i> Brain Metastases
Authors: Anuhya Kommalapati, Aaron S. Mansfield
Journal: Clinical Cancer Research (2022)

Summary The activity of KRAS inhibitors against brain metastases is relatively unexplored. The recent work on preclinical models and preliminary data from the ongoing KRYSTAL-1 phase Ib clinical trial support the potential of adagrasib (MRTX849) to penetrate the central nervous system and provide control of KRASG12C brain metastases. See related article by Sabari et al., p. 3318
Retraction Notice to: METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing
Authors: Xiaoxiang Chen, Mu Xu, Xueni Xu, Kaixuan Zeng, Xiangxiang Liu, Li Sun, Bei Pan, Bangshun He, Yuqin Pan, Huiling Sun, Xinyi Xia, Shukui Wang
Journal: Molecular Therapy (2022)

Main text(Molecular Therapy 28, 599–612, February 2020)Molecular Therapy is retracting this article. After receiving an email from one of the authors, evidence for image duplication in identical or altered fashion in Figures 2D, 3D, 4B, 4C, 4D, 8C, S2A, S2C, S3A, S3B, S3C, S4A, and S4C was identified. This reuse (and in part, misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors do not agree to the retraction. Main text(Molecular Therapy 28, 599–612, February 2020)Molecular Therapy is retracting this article. After receiving an email from one of the authors, evidence for image duplication in identical or altered fashion in Figures 2D, 3D, 4B, 4C, 4D, 8C, S2A, S2C, S3A, S3B, S3C, S4A, and S4C was identified. This reuse (and in part, misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors do not agree to the retraction. (Molecular Therapy 28, 599–612, February 2020) Molecular Therapy is retracting this article. After receiving an email from one of the authors, evidence for image duplication in identical or altered fashion in Figures 2D, 3D, 4B, 4C, 4D, 8C, S2A, S2C, S3A, S3B, S3C, S4A, and S4C was identified. This reuse (and in part, misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors do not agree to the retraction. RETRACTED: METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 ProcessingChen et al.Molecular TherapyNovember 20, 2019In BriefThis article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). Full-Text PDF Open Access
Cucurbitacin B-induced G2/M cell cycle arrest of conjunctival melanoma cells mediated by GRP78–FOXM1–KIF20A pathway
Authors: Jinlian Wei, Xin Chen, Yongyun Li, Ruoxi Li, Keting Bao, Liang Liao, Yuqing Xie, Tiannuo Yang, Jin Zhu, Fei Mao, Shuaishuai Ni, Renbing Jia, Xiaofang Xu, Jian Li
Journal: Acta Pharmaceutica Sinica B (2022)

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a Kd value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.
Advanced Achalasia Mimicking Delayed Gastric Emptying During Standard Gastric Emptying Scintigraphy
Authors: Chenxi Wu, Lance T. Hall, David C. Brandon
Journal: Clinical Nuclear Medicine (2022)

Abstract An 82-year-old man underwent outpatient nuclear medicine gastric-emptying scintigraphy (GES) for dysphagia and regurgitation. Standard solid-meal GES showed significant elongated tracer retention with calculated 96% retention rate at 3 hours, with a presumed diagnosis of delayed gastric emptying. Subsequent CT of the chest and abdomen and upper gastrointestinal fluoroscopy instead showed normal size and function of the stomach but an enormously dilated esophagus with food debris, compatible with achalasia. Attention should be made on the location and shape of the visualized “stomach” and recognize that significantly dilated esophagus can mimic an elongated stomach during GES.
Carbohydrate-based drugs launched during 2000−2021
Authors: Xin Cao, Xiaojing Du, Heng Jiao, Quanlin An, Ruoxue Chen, Pengfei Fang, Jing Wang, Biao Yu
Journal: Acta Pharmaceutica Sinica B (2022)

Carbohydrates are fundamental molecules involved in nearly all aspects of lives, such as being involved in formating the genetic and energy materials, supporting the structure of organisms, constituting invasion and host defense systems, and forming antibiotics secondary metabolites. The naturally occurring carbohydrates and their derivatives have been extensively studied as therapeutic agents for the treatment of various diseases. During 2000 to 2021, totally 54 carbohydrate-based drugs which contain carbohydrate moities as the major structural units have been approved as drugs or diagnostic agents. Here we provide a comprehensive review on the chemical structures, activities, and clinical trial results of these carbohydrate-based drugs, which are categorized by their indications into antiviral drugs, antibacterial/antiparasitic drugs, anticancer drugs, antidiabetics drugs, cardiovascular drugs, nervous system drugs, and other agents.
Retraction Notice to: Role of HCP5-miR-139-RUNX1 Feedback Loop in Regulating Malignant Behavior of Glioma Cells
Authors: Hao Teng, Ping Wang, Yixue Xue, Xiaobai Liu, Jun Ma, Heng Cai, Zhuo Xi, Zhen Li, Yunhui Liu
Journal: Molecular Therapy (2022)

Main text(Molecular Therapy 24, 1806–1822; October 2016)Molecular Therapy is retracting this article. After investigating concerns of image duplication raised by a reader, the editors identified evidence for image manipulation in altered fashion in Figures 3B, 6B, and 8B. This reuse (and in part misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors have not agreed to retract the paper and maintain that the issues identified did not affect the major conclusions of the article. Main text(Molecular Therapy 24, 1806–1822; October 2016)Molecular Therapy is retracting this article. After investigating concerns of image duplication raised by a reader, the editors identified evidence for image manipulation in altered fashion in Figures 3B, 6B, and 8B. This reuse (and in part misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors have not agreed to retract the paper and maintain that the issues identified did not affect the major conclusions of the article. (Molecular Therapy 24, 1806–1822; October 2016) Molecular Therapy is retracting this article. After investigating concerns of image duplication raised by a reader, the editors identified evidence for image manipulation in altered fashion in Figures 3B, 6B, and 8B. This reuse (and in part misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors have not agreed to retract the paper and maintain that the issues identified did not affect the major conclusions of the article. RETRACTED: Role of HCP5-miR-139-RUNX1 Feedback Loop in Regulating Malignant Behavior of Glioma CellsTeng et al.Molecular TherapyOctober, 2016In BriefThis article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). Full-Text PDF Open Archive
Effect of Timing and Coordination Training on Mobility and Physical Activity Among Community-Dwelling Older Adults
Authors: Jennifer S. Brach, Subashan Perera, Valerie Shuman, Alexandra B. Gil, Andrea Kriska, Neelesh K. Nadkarni, Bonny Rockette-Wagner, Rakie Cham, Jessie M. VanSwearingen
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Standard exercise interventions targeting underlying physiologic system impairments have limited success in improving walking. Augmenting standard interventions with timing and coordination training, which incorporates the principles of motor learning and integrates multiple systems, may be more successful. <h3>Objective</h3> To determine whether a standard strength and endurance program incorporating timing and coordination training (standard-plus) improves gait speed more than strength and endurance training alone. <h3>Design, Setting, and Participants</h3> The Program to Improve Mobility in Aging (PRIMA) study was an assessor-blinded, randomized, 2-group intervention trial that included a 12-week intervention and 24-week follow-up period. The trial was conducted at a university research clinic from 2016 to 2020. Participants included 249 community-dwelling older adults (aged ≥65 years) with gait speed between 0.60 and 1.20 m/s. Statistical analysis was performed from December 2020 to March 2021. <h3>Interventions</h3> Participants were randomized to standard strength and endurance (n = 125) or standard-plus, including timing and coordination training (n = 124), 50 to 60 minutes, twice a week for 12 weeks. <h3>Main Outcomes and Measures</h3> Primary outcome of gait speed and secondary outcomes representing components of the intervention (leg strength and power, 6-minute walk test, chair sit-and-reach test, and figure of 8 walk test) and activity and participation (Late Life Function and Disability Instrument and daily physical activity measured by accelerometry) were measured at 12, 24, and 36 weeks. <h3>Results</h3> Among 249 randomized participants, 163 (65.5%) were female, 22 (8.8%) were Black, 219 (88.0%) were White; mean (SD) age was 77.4 (6.6) years; mean (SD) gait speed was 1.07 (0.16) m/s; and 244 (98.0%) completed the intervention. The 2 groups did not have significantly different improvements in gait speed or secondary outcomes representing the components of the intervention at any time point. For gait speed, individuals in the standard-plus group had a mean (SD) improvement of 0.079 (0.135) m/s over 12 weeks, 0.065 m/s (0.141) over 24 weeks, and 0.059 (0.150) m/s over 36 weeks; individuals in the standard group improved gait speed by 0.081 (0.124) m/s over 12 weeks, 0.051 (0.129) m/s over 24 weeks, and 0.065 (0.148) m/s over 36 weeks. <h3>Conclusions and Relevance</h3> This randomized clinical trial found no difference in gait speed change between the standard and standard-plus intervention groups, and both groups showed sustained improvements in mobility 24 weeks after the intervention. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02663778
The NHS in England should use horizontal networks rather than vertical structures to improve health and care
Authors: Chris Ham
Journal: BMJ (2022)

The NHS in England should use horizontal networks rather than vertical structures to improve health and care Chris Ham co-chairThe NHS passed a landmark on 19 May 2022 when its national leaders in England announced a reduction from a level 4 (national) incident to a level 3 (regional) incident in the covid-19 response. 1840 days have passed since a national incident was first declared at the beginning of the pandemic.In that time the NHS has treated 730 000 patients with covid-19 in hospitals and delivered 123 million vaccines.Staff in all parts of the NHS have contributed with support from volunteers, the military, other public sector organisations, the private sector, and voluntary and community sector organisations.
Solitary Splenic Metastasis From Endometrial Carcinoma Revealed on FDG PET/CT
Authors: Liu Xiao, Yuhao Li, Lin Li
Journal: Clinical Nuclear Medicine (2022)

Abstract Solitary splenic metastasis from endometrial carcinoma is rare. We report a case of imaging findings of solitary splenic metastasis in a 53-year-old woman who underwent resection surgery of endometrial carcinoma of uterus 1 year ago. On FDG PET/CT, it presented as a solitary soft tissue mass with an SUVmax of 18.44. The postoperative pathology supported metastasis from endometrial carcinoma.
Non-oxidative pentose phosphate pathway controls regulatory T cell function by integrating metabolism and epigenetics
Authors: Qi Liu, Fangming Zhu, Xinnan Liu, Ying Lu, Ke Yao, Na Tian, Lingfeng Tong, David A. Figge, Xiuwen Wang, Yichao Han, Yakui Li, Yemin Zhu, Lei Hu, Yingning Ji, Nannan Xu, Dan Li, Xiaochuan Gu, Rui Liang, Guifang Gan, Lifang Wu, Ping Zhang, Tianle Xu, Hui Hu, Zeping Hu, Huji Xu, Dan Ye, Hui Yang, Bin Li, Xuemei Tong
Journal: Nature Metabolism (2022)